Constraining pesticide resistance using evolution-informed selection regimes

The rapid evolution of pesticide resistance in sexually reproducing pests threatens global food security, yet the evolutionary principles needed to design durable resistance management strategies remain poorly tested experimentally. Theory predicts that deploying multiple pesticide compounds simultaneously should suppress resistance more effectively than sequential rotations, but empirical support in sexual pest populations has remained inconclusive. Here, we directly test how selection regime shapes resistance evolution using a genetically defined, obligately mating Caenorhabditis elegans system. We evolved large dioecious populations from a near-isogenic ancestor carrying two major-effect resistance alleles under contrasting pesticide deployment regimes. We show that compound mixtures combined with a substantial refuge consistently produced the strongest constraint on resistance evolution, markedly slowing the spread of resistance even when resistance alleles were neither recessive nor rare. Species-agnostic computational simulations reproduced the overall evolutionary dynamics, suggesting broad applicability. Overall, our results provide direct experimental evidence that pesticide resistance evolution can be predictably constrained by manipulating selection regimes.